DESCRIPTION: Rates of progression vary widely among patients with chronic renal failure. In most series, at least 15% of patients do not progress at all for years; at the other extreme, some patients lose glomerular filtration rates (GFR's) as rapidly as three ml/min/mo. Previous studies, entitled "Modification of Diet in Renal Disease (MDRD)," have randomized 925 patients to various diets and blood pressure targets and followed them for an average of two years with sequential GFR's. This data set is unique in having documented greater than 6,000 GFR's. Multivariate analysis of the determinants of rates of progression among these patients has so far been able to account for no more than a small proportion of the variability in observed rates of progression. In another series of 104 patients, the applicant has identified four analyses whose levels correlate strongly with rates of progression: serum free tryptophan, serum dehydroepiandrosterone sulfate, urinary nitrate, and urinary 17-hydroxycorticosteroids. They propose to measure these analyses plus serum transforming growth factors in frozen samples from the feasibility and full-scale MDRD studies, and to determine by regression techniques how much of the observed variability in progression rates can be accounted for by these analyses. The extent to which this predictive power is independent of presently identified predictors of renal disease progression will be studied. They will also determine whether these analyses were altered by the dietary and blood pressure interventions of the MDRD studies, and the extent to which these analyses explain the observed association of achieved blood pressure and achieved protein intake with progression. The applicant indicates that the results will have important implications for the understanding the pathogenesis of progression and may point to new therapeutic approaches to slowing progression.